Diabetes is a disease with a morbidly elevated blood sugar level, and classified into type 1 diabetes that is caused by insulin depletion due to destruction of pancreatic β cells for some reason, and type 2 diabetes that is caused by impossibility of regulating the blood sugar level despite presence of insulin in the blood. Insulin regulates the blood sugar level by accelerating intake of glucose in skeletal muscle, or suppressing gluconeogenesis in the liver, or accelerating synthesis of glycogen. Glucagon-like peptide-1 (GLP-1) is secreted into blood vessels from L cells existing in the lower small intestine and in the large intestine, and binds with a GLP-1 receptor on a pancreatic β cell, to accelerate insulin secretion. Dipeptidyl peptidase IV (DPPIV) inactivates a target protein by recognizing alanine or proline at the second position from the N terminal of the protein and cutting off the two amino acids. The secreted GLP-1 is inactivated by DPPIV, and only 10 to 15% enters the systemic circulation from the liver through the portal vein (Non-Patent Document 1). Therefore, by inhibiting DPPIV or by accelerating GLP-1 secretion, insulin secretion is accelerated, and the blood sugar level decreases. Hence, a DPPIV inhibitor and a GLP-1 secretion accelerator are recently focused as a therapeutic agent or a preventive agent for diabetes.
As a DPPIV inhibitor, various synthetic pharmaceutical products including sitagliptin are known. However, these are developed in a quest to achieve high drug efficacy primarily for therapy of diabetes, and are associated with side effects such as hypoglycemia. So, peptides obtained by degrading materials for food or drink are conceived. Although these peptides are not so excellent in DPPIV inhibitory activity as synthetic pharmaceutical products, they are very useful in that safety on the human body is ensured, and a side effect will not occur even when they are regularly taken.
Mixtures containing degradation products of materials for food or drink having DPPIV inhibitory activity are described, for example, in the following Patent Documents.
Patent Document 1 describes about a preparation derived from a material for food or drink containing collagen. However, it fails to describe about with what enzyme or in what hydrolysis condition the collagen is degraded to prepare the collagen peptide mixture described in the examples, and lacks any description about what kind of peptide is contained in the collagen peptide mixture.
Patent Document 2 describes that a mixture of degradation products obtained by treating collagen or gelatin with collagenase or the like, followed by treatment with protease has DPPIV inhibitory activity. However, the protease does not have amino peptidase N activity or prolyl tripeptidyl amino peptidase activity possessed by the enzyme used in the second-step enzymatic treatment of the present invention. It also lacks the description about what kind of peptide is contained in the mixture of protease degradation products.
On the other hand, a peptide having DPPIV inhibitory activity is described in the following literatures.
Patent Document 3 describes that twenty-four peptides contained in a water-soluble fraction of cheese have DPPIV inhibitory activity. However, these peptides are long peptides containing five or more amino acids except for one peptide. Patent Document 4 describes that Gly-X-Y-(Gly-Z-W)n (n is an integer of 0 to 4, X is Pro or Leu, and Y, Z and W each independently represent any amino acids which may be the same or different (excluding Gly)) and the like which are peptides obtained by treating collagen or gelatin with collagenase or the like have DPPIV inhibitory activity. However, these peptides are long peptides containing five or more amino acids except for one peptide. Non-Patent Document 2 describes that a dipeptide and a tripeptide containing proline have DPPIV inhibitory activity, and reports that a dipeptide containing a hydrophobic amino acid on the N terminal side, in particular, has high activity.
The above peptides have a problem of poor intestinal absorptivity.
A mixture containing degradation products of a material for food or drink having GLP-1 secretion accelerating activity is described, for example, in the following literatures.
Patent Document 5 describes about a mixture of papain-degraded products of soybean protein. Non-Patent Document 3 describes that a mixture of hydrolysates of egg protein has GLP-1 secretion accelerating activity, but a mixture of hydrolysates of other proteins failed to exhibit GLP-1 secretion accelerating activity. Non-Patent Document 4 describes a mixture of hydrolysates of whey and casein. Non-Patent Documents 5 and 6 describe that a mixture of hydrolysates of zein originating from corn has GLP-1 secretion accelerating activity and DPPIV inhibitory activity, and the mixture is expected to contain a peptide having GLP-1 secretion accelerating activity and a peptide having DPPIV inhibitory activity.
However, there is no description about what kind of peptide is contained in these mixtures. These literatures lack the description of using collagen as a material for food or drink.